Investigation shows drug maker downplayed risk

Doris BloodsworthThe Orlando Sentinel

Published Sunday, November 30, 2003

Editor's note: Part two in five-part series

ORLANDO -- In November 2001, Florida Attorney General Bob Butterworth opened an investigation into the prescription painkiller OxyContin after calling it "a major threat to public health." He was concerned that Purdue Pharma's marketing of the drug may have contributed to accidental overdoses and widespread addiction -- and even told a group of doctors that he wanted to ban it.

A year later Butterworth closed his investigation, praising OxyContin as "one of the most remarkable and most prescribed painkillers in the nation today."

What happened to the probe? In the end it was little more than a paper-gathering exercise, even in the midst of mounting evidence reported by the state of overdoses and deaths linked to OxyContin. A single state investigator interviewed only a few people.

Purdue never turned over all the records the attorney general wanted. But the records that were produced suggest that Butterworth's office missed an opportunity. The documents indicate that Purdue minimized the potential dangers of OxyContin while pushing broader use of the drug, boosting sales from about $50 million in 1996 to nearly $1.5 billion in 2001.

But Purdue was never called to account. In a settlement that ended the probe on Nov. 1, 2002, the company offered $2 million toward a prescription-tracking system for Florida, and Butterworth promised that Florida would never sue the company for any actions up to the time of the settlement.

Butterworth also said the agreement with Purdue did not mean "the issues were over with for the pharmaceutical company."

He said that before he left office he wanted to gain as much as possible from Purdue and then "pass the baton" to the other states, such as Connecticut, that continue to investigate the company.

"There was delay, delay, delay," Butterworth said about trying to get records from the company. "We were losing lots of lives. Somebody had to break the ice, and we made the first major inroads."

Former Assistant Attorney General Dave Aronberg, the initial lead investigator, said Purdue benefited from timing in the state's probe. He and Butterworth were both running campaigns for state Senate seats in 2002.

The attorney general's investigation contained documents that showed the company aggressively promoted OxyContin, a time-release medication with the same potential for abuse and addiction as morphine.

The newspaper obtained 5,000 pages of records from the Fort Lauderdale, Fla. office of the attorney general. Included in the files were seven years of Purdue's marketing plans, which the company went to court to try to keep secret. The Sentinel sought to keep them public records, and a judge agreed.

Among the attorney general's records:

More than 600 "adverse event" reports from patients and doctors to the U.S. Food and Drug Administration, detailing medical problems they attributed to OxyContin -- including nausea, dizziness, shortness of breath, stupor, hallucinations, addiction and death.

A Purdue-funded study that challenges the company's own claim that addiction to opioids such as OxyContin is rare -- "less than 1 percent." Dr. Lawrence Robbins, who runs an Illinois headache clinic, found in the study that 13 percent of his chronic-headache patients became addicted to the OxyContin he prescribed.

Statements by a Purdue attorney who said there had been no studies of the drug's potential for addiction, calling them unnecessary.

Details of expense-paid trips to golf resorts used to recruit doctors paid by Purdue to talk to their colleagues about the benefits of OxyContin. Although such practices might have been common for other drugs, health-care professionals said they were inappropriate for Schedule II narcotics, which have a high potential for abuse.

Samples of Purdue's strategy to push OxyContin as a replacement for less-potent and less-abused drugs. The company handed out pens that included conversion tables that showed doctors how to switch from other medications to OxyContin. Purdue's marketing slogan was "OxyContin -- the one to start with and stay with."

Documents showing the training materials and bonus plans of the company's sales force. In a case involving a Palm Beach County, Fla. doctor, a deposition revealed that a Purdue sales representative doubled her commission from $50,000 to $100,000 between 1999 and 2000. One of her top-prescribing doctors, who is accused of overprescribing OxyContin to his patients, now faces first-degree murder and trafficking charges.

Allegations by a former Purdue employee who claimed the company's sales force had used unauthorized material to promote OxyContin. William Gergely, the company's district manager for western Pennsylvania and West Virginia for 27 years, said Purdue furnished him with materials he did not think were approved by the FDA. Gergely, who was fired in 2000 over a disputed harassment issue, was the only one of about 100 former or current Purdue employees Florida investigators contacted.

Purdue spokesman Jim Heins said the company had looked at the allegations attributed to Gergely and found "they have absolutely no merit."

Marketing plans from 1995 to 2002 that laid out the company's strategy for promoting OxyContin. In recent years, Purdue spent more than $150 million to market the painkiller. The annual reports made it clear that profit was a big part of the company's desire to expand use of its medication beyond the cancer patients originally targeted.

Marketing had been the focus of the investigation, and Butterworth said he was especially incensed about one item that he thought was aimed at patients. It was a compact disc of big-band music that showed an elderly couple dancing on the cover over the words "Swing in the right direction with OxyContin."

In a May 2002 directive, the U.S. Drug Enforcement Administration said that "direct-to-consumer advertising of controlled substances not only stimulates more than legitimate demand for drugs but may intensify the problems of diversion and abuse."

Aronberg outlined other examples of Purdue's "aggressive marketing" in a May 2002 memo to Butterworth.

"Purdue Pharma removed the warning 'May be habit forming' from the OxyContin label on Dec. 4, 1998, despite the existence of clinical studies that said the opposite," Aronberg wrote. "This warning was not reinstated until July 2001, after many deaths involving OxyContin."

Purdue said through its spokesman Heins that the FDA issued a 1998 directive for all manufacturers of controlled substances that indicated the warning was not required in the labeling if the habit-forming characteristics of the drug were described in the package insert.

"The FDA-approved package insert for OxyContin Tablets has always had clear warnings about abuse liability and dependence," Heins wrote. "Purdue has not reinstated the 'Warning -- may be habit forming' language."

Aronberg also mentioned other problems: a Purdue pamphlet that characterized addiction among opioid patients with moderate to severe pain as a myth, and a Purdue advertisement in a medical journal that federal administrators banned because it made "false or misleading" claims about treating arthritis with OxyContin.

Butterworth said he had a "contentious" meeting with Purdue officials during which he threatened them with subpoenas if they didn't turn over marketing plans the state requested. The company sent the plans along with a demand that they be kept secret.

Shortly after that Tallahassee meeting, Aronberg left to run his successful campaign for state senator. Purdue pressed the state to end its investigation, offering $2 million toward the prescription-tracking system, double the amount Butterworth had requested. The state promised never to sue the company for any actions up to Nov. 1, 2002, when the agreement was signed.

That day was a Friday; Butterworth left office the following Monday because of term limits. The next day, he lost his first election in 30 years.

Purdue counsel Udell praised the settlement.

"This is something that we eagerly and voluntarily are doing," he said. "We're doing this because we care about our patients."

Legislators have twice failed to approve the plan for the prescription-monitoring system. Reasons offered by legislators and other insiders range from end-of-session political squabbling to concerns about privacy issues.

Butterworth, Aronberg and Collins, who took over the investigation after Aronberg left, say they made the best deal possible. They say the inquiry failed to turn up anything significant. They also said Purdue had stopped many of its objectionable practices.

"We didn't find any smoking gun," Collins said, echoing Butterworth.

As controversy about OxyContin has grown nationwide, Purdue Pharma voluntarily has taken steps in a number of areas. The company has destroyed marketing props, such as the compact discs and videotapes of patient testimonials. And it has come up with a 10-point plan to try to stop abuse and diversion of OxyContin. Diversion is the rerouting of drugs from medical to illegal uses.

As part of the plan, Purdue furnished tamper-resistant prescription pads and created radio ads against prescription-drug abuse that were aimed at teenagers.

Aronberg, who went on to win praise as a freshman senator, said the ad campaign would have been better aimed at middle-aged adults, who make up the vast majority of OxyContin patients, addicts and overdose cases in Florida.

"If they can do it for young people, they can do it for middle-aged people," he said. "But it would cut into their bottom line, I think, if you tell your target audience, 'Hey, this could kill you,' or at least, 'Don't abuse it.' "

Addiction is often misunderstood, and not everyone agrees on the same definition. There is general agreement that addiction is a brain disease characterized by craving and loss of control.

In its investigation, the state failed to question claims of 1 percent addiction rates for opioids -- a mantra that is repeated throughout the medical community.

National researchers say there have been no long-term studies of opioids in noncancer patients. The "less than 1 percent" claims stem from several studies carried out decades before OxyContin arrived. One of the "studies" was a letter written by Dr. Herschel Jick that Purdue and others used to allay fears about addiction.

Jick of the Boston University School of Medicine told the Sentinel that the letter he co-authored in 1980 to the New England Journal of Medicine about his experience with almost 12,000 hospital patients was a large study of drug effects. Patients took as little as one narcotic pill or shot and used the drug from one to 10 days.

"We did not mean to have it used for any particular reason," Jick said.

Butterworth, dean of St. Thomas University law school in Miami, may not have been aware of those kinds of details in the 5,000-plus documents.

But Florida investigation files show at least two law firms that had looked closely at OxyContin pitched the idea of suing Purdue.

Cohen, Milstein, Hausfeld & Toll of Washington, D.C., showed the state an inch-thick draft complaint ready to be filed that blamed Purdue for the "rising number of addicts, abusers, criminals, and overdoses" in Florida. Similar allegations have been made in lawsuits in other states.

The lawyers told Butterworth that the state should hold the pharmaceutical company accountable. They cited three reasons: OxyContin had a defective design that failed to deliver enough pain medication during a 12-hour period as advertised, the company had played down the risks of addiction and Purdue had promoted the drug for inappropriate uses.

Orlando Mayor Buddy Dyer, who was a state senator at the time, played a pivotal role when a Florida team, headed by Pensacola lawyer James Corrigan, made a similar proposal.

Dyer said he became aware of the OxyContin problem while campaigning for attorney general last year. He said he arranged meetings with Corrigan's team and Butterworth and with Gov. Bush's legal counsel, Charles Canady.

"They had the meeting with Butterworth, and he said if the state was going to do anything, there would have to be a sign-off on it by the governor's office," said Dyer, who attended the May 2002 meeting.

Corrigan said his team of lawyers and a medical authority were willing to sue Purdue without a specified contingency fee.

"We said, 'We will get paid whatever the court says is reasonable.' How could they turn that down?" he said.

The governor's office did not respond to requests for comment.

The Panhandle attorney, whose team represents more than 1,000 OxyContin patients, said he thinks the explanation for not suing Purdue is simple.